The aim of this study is to continue and extend recent observations of the author that certain macrophage-tropic, non-syncytium inducing (NSI) HIV, like T cell tropic SI HIV, could induce direct killing of primary CD4+ T lymphocytes. Although amino acid variations in the V3 loop of gp120 greatly influenced the killing of CD4+ T cells by T cell tropic SI viruses, regions outside the loop appear to be more important for the killing of CD4+ T cells by macrophage-tropic, NSI viruses. Chimeric viruses will be constructed to determine regions of the HIV genome that are important for the killing of CD4+ T cells by macrophage- tropic, NSI HIV. Fine mapping of specific amino acids that are critical for this phenomenon will be performed by site-directed mutagenesis. The mechanism of CD4+ T cell killing by these viruses will also be studied. The goals of this study are to obtain a more complete understanding of HIV pathogenesis, to identify additional genetic determinants for cytopathogenicity of HIV and markers for the prognosis of AIDS.